Our long term goal is to introduce a normal beta-globin gene into a population of stem cells taken from an individual homozygous for HbS. These transformed stem cells will be reintroduced into the donor and selective pressure will be applied to allow the transformed stem cells to become a significant proportion of the total stem cell population. During the project period our goal will be to examine some of the prerequisites for achieving this long range objective. We intend to: 1. Establish conditions for the efficient transformation of stem cells. 2. Determine if cells carrying newly introduced genes express these genes. 3. Develop a system in which stem cells carrying an artificially introduced, "corrected" gene could be induced to multiply differentially in vivo, thereby repopulating the host cells producing a nondefective product.